The world's largest drug manufacturer must answer off-label promotion charges brought by a new adversary. Not FDA, with its warning letters and threats of marketing sanctions, and not the Office of the Inspector General (OIG) at Health and Human Services, which often sues for fraud, forces huge settlements, and requires companies to do business under restrictive corporate integrity agreements. Instead, the company faces a class-action civil suit from insurance companies and union welfare funds, groups that, until recently, Pfizer regarded primarily as customers—or at least people who picked up the tab for customers. Now, led by the Welfare Fund of a Teamsters local from New Jersey, third-party payers are suing under RICO, the Racketeering Influenced and Corrupt Organizations Act. If their suit is successful, payers who have covered billions of dollars worth of Lipitor (atorvastatin) over the past five years will receive treble damages for the cost of off-label prescriptions. The suit may also attract the attention of OIG, because the plaintiffs are claiming that Pfizer's off-label marketing "scheme" defrauded Medicare and Medicaid. All in all, this is a very complicated lawsuit. So it is worth asking—and at least trying to answer—a few basic questions. Here are some things we wondered about when we read the complaint filed in The Welfare Fund of Teamsters Local 863 v. Pfizer Inc.

All of the Lipitor prescriptions referenced in this lawsuit were written to lower LDL cholesterol.How can anyone call that off-label prescribing?

Read the label. The Lipitor label contains prescribing guidelines known as the ATP III guidelines—the Adult Treatment Panel III guidelines—which were developed by the National Cholesterol Education Panel, a group affiliated with the National Heart, Lung and Blood Institute. Based on two factors—a patient's risk of heart disease and how high the patient's cholesterol count is—the guidelines (on the label) recommend different courses of treatment. People with high risk of heart disease and high cholesterol go on statins like Lipitor from the beginning. But patients with low risk of heart disease and only moderately high cholesterol generally start out with TLC—therapeutic lifestyle changes, including diet and exercise. The lawsuit turns on these low-risk patients. The Teamsters Welfare Fund alleges that Pfizer orchestrated a far-reaching marketing campaign to convince doctors to write Lipitor prescriptions for persons at low risk of heart disease and moderate LDL cholesterol counts, whose first line of treatment would ordinarily include diet and exercise, not statin therapy. More precisely, the Lipitor label states that statins are the recommended therapy for patients with cholesterol at 130 mg/dL and two or more risk factors (such as age, smoking, hypertension, low high-density-lipid cholesterol—low HDL-C—and a family history of early coronary heart disease) if they have a 10-to-20-percent chance of suffering coronary heart disease (CHD) within the next 10 years.

However, if a patient has cholesterol of 130 mg/dL, two or more CHD risk factors, and less than a 10-percent chance of heart disease, the recommended first line of treatment is TLC. The LDL-C level "at which to consider drug therapy," for these patients, according to the label, is 160 mg/dL. When the Teamsters say Pfizer marketed Lipitor off-label, they mean that the company encouraged doctors to write Lipitor prescriptions for low-risk patients whose cholesterol is between 130 and 160 mg/dL. That is the basis for the Teamsters' fraud claim.

Whom did Pfizer harm?

No patients were harmed by off-label Lipitor prescriptions. But the Teamsters Welfare Fund, like other insurers who paid for the prescriptions, suffered financial harm when they paid for Lipitor prescriptions that, according to the complaint, never would have been written had Pfizer not marketed the drug off-label.

"Insurance companies traditionally do not require, when a GP prescribes Lipitor, a check to see if a person's cholesterol is 160," says Geoffrey Jarvis, an attorney for the plaintiffs. "The system isn't set up to sort of have that kind of Big Brother aspect to it." And Pfizer, according to the plaintiffs, took advantage of the fact that no one checked. "They got doctors to prescribe it to people who really, it's not called for," Jarvis says.